A reversible transgenic mouse model for skin cancer will be used to investigate the relationship between neoplasia and anaplasia, with the long term goal of better understanding the consequences of oncogene activation and inactivation for differentiation. The specific aims are 1) to test the hypothesis that neoplastic INV-MycERTM keratinocytes will differentiate upon removal of ectopic Myc function; 2) to identify the in vivo alterations in keratinocyte gene expression upon activation and subsequent deactivation of c-MycERTM; 3) to engineer a ubiquitously prospective, conditionally expressed, regulatable c-Myc transgenic mouse. IHC and ISH will be employed to assess the differentiation state of INV-MycERTM keratinocytes in SA1 while tissue microdissection coupled with high throughput microarray analysis will define the transcriptional basis for Myc-induced change in SA2. For SA3, the MycERTM transgene, linked by way of an IRES to EGFP and preceded by a floxed Stop cassette, will be targeted to a ubiquitously active locus by homologous recombination.